This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular disease is the most common cause of death in the industrialized world, with serious health and economic impacts. Two of the most significant forms of heart disease are ventricular and atrial fibrillation. In these arrhythmias, the normal electrical signal responsible for initiating coordinated contraction of the atria or ventricles becomes disrupted. Despite the seriousness and prevalence of cardiac fibrillation, treatment at this time is, in general, unsatisfactory, due to an incomplete understanding of how fibrillation develops and becomes sustained in the context of normal and diseased hearts. Modeling and simulation of cardiac dynamics has become an important tool for analyzing mechanisms that initiate and maintain fibrillation. Over the past several years, we have developed a set of robust computational models to perform basic research on the initiation and evolution of arrhythmias as a function of electrophysiological and anatomical properties. In this proposal we outline our plans to study important open questions, including the mechanisms for alternans in tissue;electrical control algorithms;the role of the specialized ventricular conduction system (Purkinje network) during arrhythmias;the effect of conductivity discontinuities via fiber orientation and inexcitable blood vessels on the initiation and termination of arrhythmias during electric shocks;and mechano-sensitive contributions to arrhythmogenesis.